We developed novel computer software for accurate comparison of the sequences of integral membrane proteins. The software, called AlignMe, computes sequence alignments by incorporation of membrane-protein-specific features such as hydrophobicity and transmembrane helix predictions, along with standard properties such as secondary structure, and evolutionary profiles from collections of homologous sequences M Stamm, R Staritzbichler, K Khafizov and LR Forrest, PLoS One 8(3):57731, 2013. AlignMe can be used in a number of different modes depending on the difficulty of the alignment (i.e., the similarity of the two sequences), and is particularly helpful in cases of very remote homology, because it combines sequence, secondary structure and transmembrane span predictions that help to guide the alignment of the two protein sequences. Moreover, because we use a set of known membrane protein structures as references for training of the gap penalty parameters, all AlignMe modes are perfectly tuned to aligning membrane protein sequences. We recently made the AlignMe software available via a web server hosted at www.alignme.org, providing a user-friendly interface to a diverse array of functionalities 1. The code, written in C++, can also be downloaded from that webpage and installed locally on any Unix-based platform. Notably, the AlignMe server now also provides a platform for aligning of hydropathy profiles, providing open access to a technique that was formerly only available in one or two specialized labs, but which has proven useful in a number of studies for comparison of transmembrane topologies of putatively-related proteins, including for identifying structural repeats C Fenollar-Ferrer, M Patti, T Knoepfel, A Werner, IC Forster, and LR Forrest, Biophys J 106:1268-1279, 2014; K Khafizov, R Staritzbichler, M Stamm and LR Forrest, Biochemistry 49:10702-10713, 2010.